{4-[3-isopropyl-4-methoxymethoxy-5-(4-pentylphenylethynyl)benzyl]-3,5-dimethylphenoxy}acetic acid tert-butyl ester | 446312-34-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: {4-[3-isopropyl-4-methoxymethoxy-5-(4-pentylphenylethynyl)benzyl]-3,5-dimethylphenoxy}acetic acid tert-butyl ester
• 英文别名: Tert-butyl 2-[4-[[4-(methoxymethoxy)-3-[2-(4-pentylphenyl)ethynyl]-5-propan-2-ylphenyl]methyl]-3,5-dimethylphenoxy]acetate
• CAS: 446312-34-1
• 化学式: C₃₉H₅₀O₅
• 分子量: 598.823
• InChiKey: IGEMARGRBHEMLJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.9
• 重原子数：
  44
• 可旋转键数：
  17
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  {4-[3-isopropyl-4-methoxymethoxy-5-(4-pentylphenylethynyl)benzyl]-3,5-dimethylphenoxy}acetic acid tert-butyl ester 在 盐酸 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 反应 6.0h， 生成 {4-[4-Hydroxy-3-isopropyl-5-(4-pentyl-phenylethynyl)-benzyl]-3,5-dimethyl-phenoxy}-acetic acid tert-butyl ester
  参考文献：
  名称：

  Rational Design and Synthesis of a Novel Thyroid Hormone Antagonist That Blocks Coactivator Recruitment

  摘要：

  Recent efforts have focused on the design and synthesis of thyroid hormone (T-3) antagonists as potential therapeutic agents and chemical probes to understand hormone-signaling pathways. We previously reported the development of novel first-generation T-3 antagonists DIBRT, HY-4, and GC-14 using the "extension hypothesis" as a general guideline in hormone antagonist design.(1-3) These compounds contain extensions at the 5'-position (DIBRT, GC-14) of the outer thyronine ring or from the bridging carbon (HY-4). All of these compounds have only a modest affinity and potency for the thyroid hormone receptor (TR) that limits studies of their antagonistic actions. Here, we report the design and synthesis of a novel series of 5'-phenylethynyl derivatives sharing the GC-1 halogen-free thyronine scaffold.(4) One compound (NH-3) is a T-3 antagonist with negligible TR agonist activity and improved TR binding affinity and potency that allow for further characterization of its observed activity. One mechanism for antagonism appears to be the ability of NH-3 to block TR-coactivator interactions. NH-3 will be a useful pharmacological tool for further study of T-3 signaling and TR function.

  DOI：

  10.1021/jm0201013
• 作为产物：
  描述：

  4-戊基苯乙炔 在 四丁基氟化铵 、 双(三甲基硅烷基)氨基钾 、 caesium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 21.0h， 生成 {4-[3-isopropyl-4-methoxymethoxy-5-(4-pentylphenylethynyl)benzyl]-3,5-dimethylphenoxy}acetic acid tert-butyl ester
  参考文献：
  名称：

  Rational Design and Synthesis of a Novel Thyroid Hormone Antagonist That Blocks Coactivator Recruitment

  摘要：

  Recent efforts have focused on the design and synthesis of thyroid hormone (T-3) antagonists as potential therapeutic agents and chemical probes to understand hormone-signaling pathways. We previously reported the development of novel first-generation T-3 antagonists DIBRT, HY-4, and GC-14 using the "extension hypothesis" as a general guideline in hormone antagonist design.(1-3) These compounds contain extensions at the 5'-position (DIBRT, GC-14) of the outer thyronine ring or from the bridging carbon (HY-4). All of these compounds have only a modest affinity and potency for the thyroid hormone receptor (TR) that limits studies of their antagonistic actions. Here, we report the design and synthesis of a novel series of 5'-phenylethynyl derivatives sharing the GC-1 halogen-free thyronine scaffold.(4) One compound (NH-3) is a T-3 antagonist with negligible TR agonist activity and improved TR binding affinity and potency that allow for further characterization of its observed activity. One mechanism for antagonism appears to be the ability of NH-3 to block TR-coactivator interactions. NH-3 will be a useful pharmacological tool for further study of T-3 signaling and TR function.

  DOI：

  10.1021/jm0201013

文献信息

• Rational Design and Synthesis of a Novel Thyroid Hormone Antagonist That Blocks Coactivator Recruitment
  作者：Ngoc-Ha Nguyen、James W. Apriletti、Suzana T. Cunha Lima、Paul Webb、John D. Baxter、Thomas S. Scanlan

  DOI：10.1021/jm0201013

  日期：2002.7.1

  Recent efforts have focused on the design and synthesis of thyroid hormone (T-3) antagonists as potential therapeutic agents and chemical probes to understand hormone-signaling pathways. We previously reported the development of novel first-generation T-3 antagonists DIBRT, HY-4, and GC-14 using the "extension hypothesis" as a general guideline in hormone antagonist design.(1-3) These compounds contain extensions at the 5'-position (DIBRT, GC-14) of the outer thyronine ring or from the bridging carbon (HY-4). All of these compounds have only a modest affinity and potency for the thyroid hormone receptor (TR) that limits studies of their antagonistic actions. Here, we report the design and synthesis of a novel series of 5'-phenylethynyl derivatives sharing the GC-1 halogen-free thyronine scaffold.(4) One compound (NH-3) is a T-3 antagonist with negligible TR agonist activity and improved TR binding affinity and potency that allow for further characterization of its observed activity. One mechanism for antagonism appears to be the ability of NH-3 to block TR-coactivator interactions. NH-3 will be a useful pharmacological tool for further study of T-3 signaling and TR function.